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Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine: Pharmacodynamics (PD) and Pharmacokinetics (PK)

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ClinicalTrials.gov Identifier: NCT00886886
Recruitment Status : Completed
First Posted : April 23, 2009
Last Update Posted : January 25, 2013
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Tracking Information
First Submitted Date  ICMJE April 22, 2009
First Posted Date  ICMJE April 23, 2009
Last Update Posted Date January 25, 2013
Study Start Date  ICMJE April 2009
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2009)
Effect of reboxetine on subjective responses to MDMA [ Time Frame: 24h ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2009)
  • Effect of reboxetine on physiological responses to MDMA [ Time Frame: 24h ]
  • Effects of reboxetine on pharmacokinetics of MDMA [ Time Frame: 24h ]
  • Tolerability of MDMA and reboxetine [ Time Frame: 7 days ]
  • Effect of reboxetine on neuroendocrine responses to MDMA [ Time Frame: 24h ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 24, 2013)
Genetic polymorphisms [ Time Frame: assessed after study completion ]
Effects of genetic polymorphisms on the response to MDMA
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine: Pharmacodynamics (PD) and Pharmacokinetics (PK)
Official Title  ICMJE Pharmacological Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy): Pharmacological Effects and Pharmacokinetics
Brief Summary MDMA releases dopamine, serotonin, and norepinephrine in the brain. Serotonin uptake inhibitors have been shown to interact with 3,4-Methylenedioxymethamphetamine (MDMA) and to decrease its psychoactive and cardiovascular stimulant effects. This finding indicates that MDMA acts in part by releasing serotonin through the serotonin uptake site. However, in vitro studies show that MDMA binds more potently to the norepinephrine uptake site that to the the serotonin or dopamine uptake transporter. In addition, norepinephrine uptake site blockers such antidepressant drugs attenuate some of the behavioral effects of MDMA in animals. These preclinical data indicate that norepinephrine may also contribute to the response to MDMA in humans. To test this hypothesis this study evaluates the interacting effects of the selective norepinephrine transporter inhibitor reboxetine on the subjective and cardiovascular stimulant effects of MDMA in healthy volunteers.
Detailed Description

The study will use a randomized double-blind cross-over design with four experimental sessions. Reboxetine (8 mg) or placebo will be administered the night before the experimental session and 1 h before the administration of MDMA (125 mg) or placebo to 16 healthy volunteers. Subjective and cardiovascular responses and plasma samples for pharmacokinetics will be repeatedly assessed throughout the experiments.

We hypothesize that the highly selective norepinephrine uptake inhibitor reboxetine will attenuate subjective and especially heart rate and blood pressure responses to MDMA. Such a result would indicate that norepinephrine is critically involved in the pharmacology of MDMA and may provide helpful in the use and development of treatments for Ecstasy intoxications.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE
  • Mood Disorder
  • Substance-related Disorders
  • Amphetamine-related Disorders
Intervention  ICMJE
  • Drug: MDMA
    125 mg, single dose
  • Drug: Reboxetine, 8 mg
    two doses 12h and 2h before MDMA
  • Drug: Placebo
    capsules identical to MDMA or Reboxetine
Study Arms  ICMJE Reboxetine, MDMA, Placebo
Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but two (actually 4) treatment conditions in the same subject.
Interventions:
  • Drug: MDMA
  • Drug: Reboxetine, 8 mg
  • Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 22, 2009)
16
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2010
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Sufficient understanding of the German language
  • Subjects understand the procedures and the risks associated with the study
  • Participants must be willing to adhere to the protocol and sign the consent form
  • Participants must be willing to refrain from taking illicit psychoactive substances during the study.
  • Participants must be willing to drink only alcohol-free liquids and no xanthine-containing liquids (such as coffee, black or green tea, red bull, chocolate) after midnight of the evening before the study session. Subjects must agree not to smoke tobacco for 1 h before and 4 hours after MDMA administration.
  • Participants must be willing not to drive a traffic vehicle in the evening of the study day.
  • Women of childbearing potential must have a negative pregnancy test at the beginning of the study and must agree to use an effective form of birth control. Pregnancy tests are repeated before each study session.
  • Body mass index: 18-25 kg/m2

Exclusion Criteria:

  • Chronic or acute medical condition including clinically relevant abnormality in physical exam, laboratory values, or ECG. In particular: Hypertension (>140/90 mmHg). Personal or first-grade history of seizures. Cardiac or neurological disorder.
  • Current or previous psychotic or affective disorder
  • Psychotic or affective disorder in first-degree relatives
  • Prior illicit drug use (except Tetrahydrocannabinol-containing products) more than 5 times or any time within the previous 2 months.
  • Pregnant or nursing women.
  • Participation in another clinical trial (currently or within the last 30 days)
  • Use of medications that are contraindicated or otherwise interfere with the effects of the study medications (monoamine oxidase inhibitors, antidepressants, sedatives etc.)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00886886
Other Study ID Numbers  ICMJE EKBB373/08
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University Hospital, Basel, Switzerland
Original Responsible Party Matthias Liechti, MD, Clinical Pharmacology and Toxicology University Hospital, Basel, Switzerland
Current Study Sponsor  ICMJE University Hospital, Basel, Switzerland
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Matthias E Liechti, MD Department of Internal Medicine, Division of Pharmacology & Toxicology, University Hospital Basel, Switzerland
PRS Account University Hospital, Basel, Switzerland
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP